chr6-152721813-T-C

Variant names:

• chr6-152721813-T-C
• rs2099724753
• NM_025107.3:c.268T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025107.3(MYCT1):​c.268T>C​(p.Phe90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: MYCT1 NM_025107.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.134
• Publications: 0 publications found

Genes affected

MYCT1 (HGNC:23172): (MYC target 1) Predicted to act upstream of or within hematopoietic stem cell homeostasis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03980601).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025107.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCT1	NM_025107.3	MANE Select	c.268T>C	p.Phe90Leu	missense	Exon 2 of 2	NP_079383.2	Q8N699
	MYCT1	NM_001371624.1		c.124T>C	p.Phe42Leu	missense	Exon 2 of 3	NP_001358553.1	D6Q1S4
	MYCT1	NM_001371625.1		c.124T>C	p.Phe42Leu	missense	Exon 2 of 3	NP_001358554.1	D6Q1S4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCT1	ENST00000367245.6	TSL:1 MANE Select	c.268T>C	p.Phe90Leu	missense	Exon 2 of 2	ENSP00000356214.5	Q8N699
	MYCT1	ENST00000532295.1	TSL:3	c.208T>C	p.Phe70Leu	missense	Exon 2 of 3	ENSP00000434396.1	H0YDV5
	MYCT1	ENST00000529453.1	TSL:3	c.197-950T>C		intron	N/A	ENSP00000432612.1	E9PQ55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461878 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Benign	0.37
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.32	N
PhyloP100		0.13
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.027
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.34		Gain of MoRF binding (P = 0.1138)
MVP		0.014
MPC		0.012
ClinPred		0.033	T
GERP RS		0.77
Varity_R		0.065
gMVP		0.27
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2099724753; hg19: chr6-153042948;